Health communication research in the Arab world: A bibliometric analysis.
Health communication is a novel field in the Arab world. This study aimed to describe and characterise health communication research activity in the region. The PubMed database was used to search for publications related to health communication from Arab states. Publications were classified according to country of origin, without limiting for date. Research activity and output were examined with respect to population and the gross domestic product (GDP) of each Arab state. A total of 66 contributions related to health communication came from the Arab countries, with the first paper published from Lebanon in 2004. Health communication-related publications constituted 0.03% of the total biomedical research contributions published by the Arab world since 2004 and 1% of the world's health communication literature. Number of health communication contributions ranged between 0 and 12, with Lebanon producing the most output. Qatar ranked first with respect to contributions per population, whereas Lebanon ranked first with respect to contributions per GDP. Algeria, Comoros, Djibouti, Iraq, Kuwait, Libya, Mauritania, Somalia, Sudan and Yemen had nil health communication publications. Recognising the barriers facing the health communication field and addressing them carefully are vital in the plan to better the Arab world's output and contribution in the field.


Molecular study of the Prader-Willi syndrome: deletion, RFLP, and phenotype analyses of 50 patients.
Deletion and RFLP studies with 5 cloned DNA markers localized at 15q11.2 were performed in 50 patients with the Prader-Willi syndrome (PWS). A one-copy density (deletion) for at least one of 4 loci, D15S9, D15S11, D15S10, D15S12, was detected in 32 (64%) of the 50 patients; deletions of each of the 4 loci were found in 29, 30, 29, and 28 patients, respectively. Three patients showed 4 or more copy density for D15S12 locus, in addition to deletions. The remaining 18 patients showed two-copy densities for each of the 4 loci. A common site of rearrangements among our 32 patients as well as the reported patients seemed to be confined to a segment between D15S9 and D15S11, suggesting the putative PWS gene locus in this segment. Of 6 patients who have cytologic deletions but did not show any molecular deletions, 3 have normal size of hands and feet, and 4 have normally pigmented skin and hair. The normal pigmentation was also observed in 3 patients who had small molecular deletions in the examined 5-locus segment. These observations may support the conception of contiguous gene syndrome. RFLP analysis demonstrated maternal uniparental isodisomy of chromosomes 15 in both a patient with 45,t(15q;15q) and a karyotypically normal patient. Based on the results of the present study, a new model is proposed to explain the occurrence of PWS with a variety of chromosome abnormalities, including partial monosomy, disomy, trisomy, and/or tetrasomy for 15q11.2. The normal development may require an even or more "number ratio" of paternally derived allele(s) to maternally derived allele(s) of the gene(s) localized at 15q11.2, and a disturbance of the ratio would lead to the PWS phenotype.


Tardive diskinesia: a clinical interpretation.
This paper discusses various clinical conditions with oral diskinetic movements and proposes, on the basis of clinical evidence, an interpretation of drug-induced oral diskinesia as a conditioned response to local aversive stimuli related to drug use (local side effects), or other factors such as missing teeth and ill-fitting dentures. There is an accompanying anxiety associated with the aversive stimulus or with difficulties in verbal expression, as in the case of brain damaged patients. The diskinetic movements are initially Voluntary movements aiming at removing the aversive stimulus (stage of voluntary movements). If they succeed in reducing the accompanying anxiety, the reduction of anxiety reinforces the diskinetic response. In a subsequent stage, these movements lose their laborious voluntary quality and become automatic (stage of automatic movements). In a final stage, the diskinetic movements become instrumental in reducing anxiety in the absence of the aversive stimulus (stage of instrumentalization). The question is raised whether drug-induced oral diskinesia can be placed under the general rubric of tics, as a special drug-induced form of it.


Analysis of age-dependence of the anterior and posterior cornea with scheimpflug imaging.
To assess keratometric and higher-order aberrations of the anterior and posterior cornea and their age-related changes. This study investigated one healthy eye of 227 patients (mean age: 55.15 ± 21.2 years; range: 16 to 90 years; 135 right eyes, 92 left eyes). Images were captured from each eye with Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany) using automatic mode. Keratometric, astigmatism data, and corneal higher-order aberrations were analyzed. With respect to laterality, no deviance was found in any of the parameters (P > .05). Mean refractive error was 0.52 ± 0.23 diopters. The level of astigmatism decreased significantly with advancing age for both the anterior and posterior corneal surfaces (P < .05). The overall root mean square of the higher-order aberration increased continuously with age (r = 0.517; P < .01), which can be explained by the combined effect of the increased in both the anterior and posterior corneal root mean square higher-order aberrations. Of the higher-order aberrations, the constant increase of the primary and secondary spherical aberration with aging (P < .01) is caused by the spherical aberration growth of the anterior surface. Apart from these, only the vertical coma aberration of the posterior surface and the vertical trefoil aberrations of both the anterior and posterior surfaces showed a significantly positive correlation with aging (P < .05). Corneal astigmatism showed a significant decrease with aging. Of the higher-order aberrations, primary and secondary spherical aberrations, vertical coma, and vertical trefoil significantly increase with age, whereas other higher-order aberrations show no correlation with aging.


Improved Dried Blood Spot PCR Assay for Universal Congenital Cytomegalovirus Screening in Newborns.
Congenital cytomegalovirus (cCMV) is the most common perinatal infection, the leading cause of nongenetic sensorineural hearing loss, and one of the leading causes of neurodevelopmental impairment in the developed world. Early identification via newborn screening (NBS) would benefit the many undiagnosed infants who are either asymptomatic or mildly to moderately symptomatic, of whom 20% develop sequelae. The sensitivity of a recently developed PCR-based method to detect CMV in dried blood spots (DBS) is less than 80% and requires significantly more specimen than any other NBS test. We sought to improve the analytical sensitivity of the screening method by using droplet digital PCR and direct PCR and decreasing the amount of specimen utilized. The methods were tested with CMV-spiked filters, DBS from CMV-spiked cord blood, and DBS from neonates with cCMV. The results showed that the analytical sensitivity of all modified methods was equivalent to that of the reference method, with consistent CMV detection at high viral loads and inconsistent detection at low viral loads. IMPORTANCE Implementation of screening for cCMV in public health programs is hindered by feasibility challenges, including limited specimen availability and an insufficiently sensitive DBS-based screening assay. We report on efforts to improve the currently available DBS-based molecular assay to increase its feasibility of implementation in newborn screening programs. Although the analytical sensitivity of the modified methods was similar at the lower IU, equivalent CMV detection was achieved using one punch instead of the required three punches for the reference method. This reduction in sample size has the potential to substantially improve feasibility of NBS for cCMV. A population-based study is needed to further evaluate the clinical sensitivity of the improved assay.


One-stage operation for superficialization of native radio-cephalic fistula in obese patients.
The population of obese patients is increasing in general and also at hemodialysis initiation. For successful cannulation of arteriovenous fistula, the National Kidney Foundation-Dialysis Outcome Quality Initiative guidelines suggest that the required maturation parameters are at a depth of <6 mm. There are several reports describing two-stage superficialization of arteriovenous fistulas in obese cases. Therefore, we investigated the utility and complications of one-stage superficialization of radio-cephalic fistula. From January 2011 to March 2017, we simultaneously performed forearm radio-cephalic fistula creation and superficialization of the cephalic vein for 10 patients having obesity (body mass index > 30 kg/m2) and deep cephalic vein (>6 mm). Initially, an arteriovenous anastomosis was created at an appropriate site. Subsequently, an 8-10 cm longitudinal skin incision was made along the lateral aspect of the forearm cephalic vein. The cephalic vein was identified and exposed. The cephalic vein was repositioned superficially. The mean age of the patients was 53 years (range: 40-72 years) and the mean body mass index was 40.2 kg/m2 (33.1-59.7 kg/m2). The cause of renal failure in eight patients was diabetic nephropathy, and in two patients, it was unknown. After the procedure, vein depth became 3.4 mm (1.9-4.6 mm) from 8.2 mm (6.0-13.4 mm). All patients who initiated dialysis underwent successful two-needle cannulation. Primary patency rate was 71.4% at 12 months (two patients underwent percutaneous transluminal angioplasty) and secondary patency rate was 100%. There was one procedure-related complication and delayed wound healing, which was improved by observation without antibiotics. This small series of patients indicates that one-stage superficialization of radio-cephalic fistula is a safe and effective option to start hemodialysis in obese subjects.


Cardiac involvements in hypereosinophilia-associated syndrome: Case reports and a little review of the literature.
Hypereosinophilia-associated syndrome is a rare group of systemic diseases without certain underlying causes. Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), are initial considerations, when underlying causes remains unexplained despite of complete evaluation of hypereosinophilia. In this study, we report two rare cases, one case of HES with Loeffler endocarditis, and the other one of EGPA with restrictive cardiomyopathy mimicking myocardial infarction, to further address differential chief cardiac manifestations between HES and EGPA. Key roles of echocardiography played in detection of cardiac involvements, diagnosis, and prognosis prediction are also highlighted.


Trimethoprim-sulfamethoxazole oral desensitization in hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reactions.
Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.


Site and mechanisms of action of kinins in rat ileal mucosa.
Kinin-induced secretion in the intestine is accompanied by marked increases in mucosal adenosine 3', 5'-cyclic monophosphate (cAMP) and prostanoids that undoubtedly contribute to the overall secretory response. The cellular site at which these effects are initiated is unclear although a recent hypothesis has suggested the epithelial cell as the target for kinin action (6). We have investigated the effects of kallidin on the phospholipase-prostanoid-cAMP pathway in whole ileal mucosa and in epithelial cells isolated from the same tissue in the rat. Kallidin (1 microM) stimulated a marked rise (24 to 30-fold) in PG (prostaglandin) E2 release from the serosal surface of stripped ileal mucosa within 1-2 min, which correlated closely with the rise in mucosal short-circuit current. Mucosal cAMP levels were also increased two to threefold by kallidin. However, kinins were unable to elicit effects under the same conditions in suspensions of viable epithelial cells. PGE2 release was unaffected by kallidin or bradykinin at concentrations up to 100 microM, whereas cAMP levels could be stimulated by forskolin and PGE2 but not by kinin. Studies of intestinal phospholipase A2 (PLA2) activity also suggest a nonepithelial site for kinin action. This enzyme is responsible for liberating arachidonic acid from cellular phospholipids and has been shown to be activated by kinins in several tissues. In the intestine, PLA2 activity was found to be concentrated within the subepithelium with significantly lower levels in the epithelium itself. In addition, kallidin was unable to influence phospholipid labeling (an indirect measure of PLA2 activity) in cells incubated with [14C]arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Ontogeny of the electric organs in the electric eel, Electrophorus electricus: physiological, histological, and fine structural investigations.
This study attempts to clarify the controversy regarding the ontogenetic origin of the main organ electrocytes in the electric eel, Electrophorus electricus. The dispute was between an earlier claimed origin from a skeletal muscle precursor [Fritsch, 1881], or from a distinct electrocyte-generating matrix, or germinative zone [Keynes, 1961]. We demonstrate electrocyte formation from a metamerically organized group of pre-electroblasts, splitting off the ventralmost tip of the embryonic trunk mesoderm at the moment of hatching from the egg. We show details of successive stages in the development of rows of electric plates, the electrocytes, by means of conventional histology and electron microscopy. The membrane-bound pre-electroblasts multiply rapidly and then undergo a specific mitosis where they lose their membranes and begin extensive cytoplasm production as electroblasts. Electrical activity, consisting of single and multiple pulses, was noticed in seven-day-old larvae that began to exhibit swimming movements. A separation of discharges into single pulses and trains of higher voltage pulses was seen first in 45-mm-long larvae. A lateralis imus muscle and anal fin ray muscles, implicated by earlier investigators in the formation of electrocytes, begin developing at a time in larval life when eight columns of electrocytes are already present. Axonal innervation is seen very early during electrocyte formation.


Identification of mating type loci and development of SCAR marker genetically linked to the B3 locus in Pleurotus eryngii.
In order to estimate how diverse the mating types in Pleurotus eryngii from different regions are, pairings between monokaryons derived from inter- and intragroups were done. Sixteen and 15 alleles were identified at loci A and B from the 12 strains. In the P. eryngii KNR2312, widely used for commercial production, four mating loci, A3, A4, B3, and B4, were determined. Those loci, except A3, were found in 4 strains out of 12 strains. To improve breeding efficiency, especially in mating type determination, RAPD and BSA were performed to screen for a mating type specific marker. The SCAR marker 13- 2(2100) was developed based on the RAPD-derived sequence typing B3 locus. The sequence analysis of 13-2(2100) revealed that it contained a conserved domain, the STE3 superfamily, and consensus sequences like the TATA box and GC box. It seems likely that the SCAR marker region is a part of the pheromone receptor gene.


Isolation, Structure Elucidation, and Biosynthesis of a Cysteate-Containing Nonribosomal Peptide in Streptomyces lincolnensis.
The species Streptomyces lincolnensis is known as a producer of lincomycin A, a clinically important lincosamide antibiotic with activity against Gram-positive bacteria. Here, we report that S. lincolnensis produces a new cysteate-containing lactone product, cysteoamide (1), which arises from nonribosomal peptide synthetase-programmed sequential assembly of the monomers phenylacetic acid, valine, cysteate, threonine, β-hydroxyleucine, and β-alanine and subsequent intramolecular cyclization to form a lactone ring. The structure of 1 was determined by combined analysis of NMR and MS spectra, while the amino acid absolute configurations in 1 were assigned by Marfey's analysis following acid hydrolysis. The biosynthetic gene cluster of 1 was defined in the genome of S. lincolnensis by bioinformatics analysis and in vivo genetic study. In addition, in vitro assay revealed that OrfA, a pyridoxal 5'-phosphate-dependent protein, is responsible for the formation of the unusual cysteate unit. Cysteate-containing nonribosomal peptides appear to be widely present in various Streptomyces strains, and this study generates interest in their intrinsic functions that remain poorly understood.


Absolute configuration of franganine.
The absolute configuration of franganine (1), a cyclopeptide alkaloid isolated from the methanol root bark extract of Discaria americana, was established on the basis of detailed NMR spectroscopic data and X-ray diffraction analysis of its salt (2).


Fluorescence staining of the actin cytoskeleton in living cells with 7-nitrobenz-2-oxa-1,3-diazole-phallacidin.
An active fluorescent derivative of the actin-binding mushroom toxin phallacidin has been synthesized. Convenient methods were developed to stain actin cytoskeletal structures in living and fixed cultured animal cells and actively streaming algal cells. Actin binding specificity was demonstrated by competitive binding experiments and comparative staining of well-known structures. Large populations of living animal cells in culture were readily stained by using a relatively mild lysolecithin permeabilization procedure facilitated by the small molecular size of the label. Actin in animal cells was stained stress fibers, ruffles, the cellular geodome, and in diffuse appearing distributions apparently associated with the plasma membrane. Staining of actin cables in algae with nitrobenzoxadiazole (NBD)-phallacidin did not inhibit cytoplasmic streaming. NBD-phallacidin provides a convenient actin-specific fluorescent label for cellular cytoskeletal structures with promise for use in studies of actin dynamics in living systems.


A High-Throughput Genetic Complementation Assay in Yeast Cells Identified Selective Inhibitors of Sphingosine Kinase 1 Not Found Using a Cell-Free Enzyme Assay.
Sphingosine kinase 1 (SphK1) is a lipid kinase that phosphorylates sphingosine to produce the bioactive sphingolipid, sphingosine-1-phosphate (S1P), and therefore represents a potential drug target for a variety of pathological processes such as fibrosis, inflammation, and cancer. We developed two assays compatible with high-throughput screening to identify small-molecule inhibitors of SphK1: a purified component enzyme assay and a genetic complementation assay in yeast cells. The biochemical enzyme assay measures the phosphorylation of sphingosine-fluorescein to S1P-fluorescein by recombinant human full-length SphK1 using an immobilized metal affinity for phosphochemicals (IMAP) time-resolved fluorescence resonance energy transfer format. The yeast assay employs an engineered strain of Saccharomyces cerevisiae, in which the human gene encoding SphK1 replaced the yeast ortholog and quantitates cell viability by measuring intracellular adenosine 5'-triphosphate (ATP) using a luciferase-based luminescent readout. In this assay, expression of human SphK1 was toxic, and the resulting yeast cell death was prevented by SphK1 inhibitors. We optimized both assays in a 384-well format and screened ∼10(6) compounds selected from the Boehringer Ingelheim library. The biochemical IMAP high-throughput screen identified 5,561 concentration-responsive hits, most of which were ATP competitive and not selective over sphingosine kinase 2 (SphK2). The yeast screen identified 205 concentration-responsive hits, including several distinct compound series that were selective against SphK2 and were not ATP competitive.


Age-Dependent Clinical Characteristics of Acute Lower Respiratory Infections in Young Hospitalized Children with Respiratory Syncytial Virus Infection.
Human respiratory syncytial virus (HRSV) is the most common cause of acute lower respiratory infection (LRTI) in children. The main clinical manifestations are fever, cough, wheezing, and intercostal retractions. Its age-dependent clinical characteristics remain to be defined. We investigated whether HRSV caused any age-related differences in clinical manifestations of LRTI. We enrolled 130 hospitalized children with LRTI caused by HRSV. These were stratified into four age groups. The main signs and symptoms and rates thereof were compared across the four age groups. The incidence of pneumonia was the same in all four age groups. Patients in the 1-6 months old group experienced fever and the highest body temperature ≥ 38.5°C less frequently than patients in other age groups.The frequency of fever increased with age among the patients under 24 months old. Children over 12 months old experienced less wheezing, tachypnoea, hypoxia, and intercostal retractions than children in the 1-6 months old group. HRSV caused age-related differences in clinical manifestations of LRTI. Reduced fever responses among patients 6 months old and younger during RSV infection does not implicate less severity, wheezing, tachypnoea, hypoxia, and intercostal retractions are the main clinical manifestations, Fever responses were enhanced with advancing age among children under 24 months old.


Protective effects of epigallocatechin-3-gallate against lead-induced oxidative damage.
A positive association of lead exposure with clinical cardiovascular outcomes has been identified. Epigallocatechin-3-gallate (EGCG) is one of the active polyphenols in green tea, it has not been reported as an antioxidant against lead toxicity. This study was carried out to investigate whether EGCG could protect the ventricular myocytes of rats against lead-induced oxidative damage. Isolated ventricular myocytes were exposed to lead and/or EGCG, then activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) and the levels of hydroxyl radical (OH(·)), hydrogen peroxide (H(2)O(2)), and superoxide anion (O(2) (·-)) were measured. The results showed that lead induced a significant decrease of SOD and CAT activities, while the levels of MDA increased significantly. Increases in intracellular OH(·), O(2) (·-), and H(2)O(2) were found as well. These processes were concentration-dependent and statistically significant different when compared to 2.0 µM lead exposure. The activity of SOD and CAT increased while the levels of MDA and reactive oxygen species (ROS) decreased after treatment with EGCG. While there were progressive benefits with increasing EGCG concentrations, there was no statistical significance at a 30 µg/mL dose when compared with the control. These results will provide more evidence for lead toxicity to tissue, cell, and biological macromolecule.


Parents living with a child afflicted by a life-limiting medical condition: Typology of their narrative identity.
Parents of children suffering from a life-limiting medical condition struggle with difficult existential questions. Our objective was to understand why those parents' interactions with the medical world were so different, ranging from hostile to collaborative, with the themes of identity, spirituality and serenity. A grounded theory design based on the narrative identity framework was used to interview sixteen parents. Three categories emerged: i) Parents in the Almighty category delegate all their power to God or medicine and are the most suffering parents as they do not author their life; ii) Parents in the Me category make every decision on their own causing much anxiety, and they become rebarbative to the medical world; iii) Parents in the Guide category take advice from others, while remaining the authors of their stories and are the most serene parents. Understanding and recognizing these categories can have a major impact on communication with those families.


Effect of suturing technique on corneal xenograft survival.
Understanding xenograft rejection is crucial for the potential introduction of xenotransplantation into clinical practice. Small-animal models play an essential role in this context and substantially contribute to our knowledge about mechanisms of xenograft rejection. Rat-to-mouse corneal xenografts were performed by using 2 suturing techniques. Sutures were left either as long or as short as possible to limit the extent of a nonspecific inflammatory response. Cyclosporine A (CsA), monoclonal antibody anti-T cells, and a specific inhibitor of inducible NO synthase (alone or in a combination with CsA) were tested as immunosuppressants. Grafts with long sutures were rejected in 7.3 +/- 1.2 days, whereas those with short sutures were rejected after 11.8 +/- 1.0 days (P < 0.001). Similarly, long sutures induced more pronounced corneal neovascularization (P < 0.001). Although groups of recipients with long sutures all tested immunosuppressants significantly (P < 0.01-0.001) prolonged corneal graft survival, none of them showed a comparable efficacy in groups of recipients with short sutures. This study showed that suturing technique significantly affects the outcome of corneal concordant xenograft transplantation, influences the effectiveness of immunosuppressive regimens, and therefore must be taken into account when evaluating their efficacy.


"Healthcare should be the same for everyone": perceived inequities in therapeutic trajectories of adult patients with lung cancer in Chile, a qualitative study.
Globally, it has been reported that different social determinants of health affect health outcomes in lung cancer (LC). Research on the therapeutic trajectories of patients (TTP) is a novel field for identifying barriers and facilitators in health. The objective of this study was to reveal perceived differences in TTP with LC in Chile according to selected social determinants of health (SDH) and the experiences of patients, health professionals, and civil society leaders. This is a qualitative paradigm, one case-study design. Online semi-structured interviews were conducted with patients with LC, health professionals, and civil society leaders. The strategies for the recruitment process included social networks, civil society organizations, health professionals, and the snowball technique. A thematic analysis was carried out. Selected SDH impact LC's TTP in Chile, particularly concerning health system access, health services, information, and patient navigation experiences. The analysis of the experiences of the participants allowed us to identify barriers related to the selected SDH in three stages of the TTP: initiation, examinations, and diagnosis and treatment. Individuals with limited education, those residing outside the capital, women, and those in the public health system encountered more barriers throughout their TTP. Study findings suggest that being a woman with low education, from the public health system, and not from the capital might represent one of the most powerful intersections for experiencing barriers to effective healthcare in LC in Chile. It is necessary to monitor the TTP from an SDH perspective to guarantee the rights of access, opportunity, quality, and financial protection.


Altered placental ion channel gene expression in preeclamptic high-altitude pregnancies.
High-altitude (>2,500 m) residence increases the risk of pregnancy vascular disorders such as fetal growth restriction and preeclampsia, each characterized by impaired placental function. Genetic attributes of highland ancestry confer relative protection against vascular disorders of pregnancy at high altitudes. Although ion channels have been implicated in placental function regulation, neither their expression in high-altitude placentas nor their relationship to high-altitude preeclampsia has been determined. Here, we measured the expression of 26 ion-channel genes in placentas from preeclampsia cases and normotensive controls in La Paz, Bolivia (3,850 m). In addition, we correlated gene transcription to maternal and infant ancestry proportions. Gene expression was assessed by PCR, genetic ancestry evaluated by ADMIXTURE, and ion channel proteins localized by immunofluorescence. In preeclamptic placentas, 11 genes were downregulated (ABCC9, ATP2A2, CACNA1C, KCNE1, KCNJ8, KCNK3, KCNMA1, KCNQ1, KCNQ4, PKD2, and TRPV6) and two were upregulated (KCNQ3 and SCNN1G). KCNE1 expression was positively correlated with high-altitude Amerindian ancestry and negatively correlated with non-high altitude. SCNN1G was negatively correlated with African ancestry, despite minimal African admixture. Most ion channels were localized in syncytiotrophoblasts (Cav1.2, TRPP2, TRPV6, and Kv7.1), whereas expression of Kv7.4 was primarily in microvillous membranes, Kir6.1 in chorionic plate and fetal vessels, and MinK in stromal cells. Our findings suggest a role for differential placental ion channel expression in the development of preeclampsia. Functional studies are needed to determine processes affected by these ion channels in the placenta and whether therapies directed at modulating their activity could influence the onset or severity of preeclampsia.


Identification of the thiol isomerase-binding peptide, mastoparan, as a novel inhibitor of shear-induced transforming growth factor β1 (TGF-β1) activation.
TGF-β1 is a disulfide-bonded homodimeric protein produced by platelets and other cells that plays a role in many physiologic and pathologic processes. TGF-β1 is secreted as an inactive large latent complex (LLC) comprised of TGF-β1, latency-associated peptide, and latent TGF-β binding protein 1. We previously demonstrated that shear force can activate LLC and that thiol-disulfide exchange contributes to the process. We have now investigated the role of thiol isomerases in the activation of LLC in platelet releasates (PR) and recombinant LLC. The wasp venom peptide mastoparan, which inhibits the chaperone activity of PDI, inhibited stirring- and shear-induced activation of latent TGF-β1 by 90 and 75% respectively. To identify the proteins that bind to mastoparan either directly or indirectly, PR were chromatographed on a mastoparan affinity column. Latent TGF-β binding protein 1, latency-associated peptide, TGF-β1, clusterin, von Willebrand factor, multimerin-1, protein disulfide isomerase (PDI), ERp5, ERp57, and ERp72 eluted specifically from the column. Anti-PDI RL90 attenuated the inhibitory effect of mastoparan on LLC activation. Furthermore, reduced PDI inhibited activation of PR LLC, whereas oxidized PDI had no effect. We conclude that thiol isomerases and thiol-disulfide exchange contribute to TGF-β1 activation and identify a number of molecules that may participate in the process.


Development, Validation, and Application of a Novel Method for the Analysis of Vitamin E Acetate and Other Tocopherols in Aerosol Emissions of E-Cigarettes, or Vaping Products Associated With Lung Injury.
E-cigarette, or vaping, product (EVP) use has increased dramatically in the United States over the last 4 years, particularly in youth and young adults. Little information is available on the chemical contents of these products. Typically, EVPs contain an active ingredient such as nicotine, CBD, or THC dissolved in a suitable solvent that facilitates aerosol generation. One EVP solvent, vitamin E acetate (VEA), has been measured in EVP liquids associated with lung injury. However, no validated analytical methods for measuring VEA in the aerosol from these devices was previously available. Therefore, we developed a high throughput isotope dilution LC-MS/MS method to simultaneously measure VEA and three other related tocopherols in aerosolized EVP samples. The assay was precise, with VEA repeatability ranging from 4.0 to 8.3% and intermediate precision ranging from 2.5 to 6.7%. Similar precision was obtained for the three other tocopherols measured. The LODs for the four analytes ranged from 8.85 × 10-6 to 2.28 × 10-5 μg analyte per mL of aerosol puff volume, and calibration curves were linear (R 2 > 0.99). This method was used to analyze aerosol emissions of 147 EVPs associated with EVALI case patients. We detected VEA in 46% of the case-associated EVPs with a range of 1.87 × 10-4-74.1 µg per mL of aerosol puff volume and mean of 25.1 µg per mL of aerosol puff volume. Macro-levels of VEA (>0.1% w/w total aerosol particulate matter) were not detected in nicotine or cannabidiol (CBD) products; conversely 71% of the EVALI associated tetrahydrocannabinol (THC) products contained macro-levels of VEA. Trace levels of other tocopherol isoforms were detected at lower rates and concentrations (α-tocopherol: 41% detected, mean 0.095 µg analyte per mL of aerosol puff volume; γ-tocopherol: 5% detected, mean 0.0193 µg analyte per mL of aerosol puff volume; δ-tocopherol: not detected). Our results indicate that VEA can be efficiently transferred to aerosol by EVALI-associated EVPs vaped using a standardized protocol.


2,5-Dimethyl-2'-hydroxy-9 alpha- and 9 beta-(3-methylbutyl)-6,7-benzomorphans and N-substituted compounds in the 9 alpha-(3-methylbutyl) series: chemistry, pharmacology, and biochemistry.
2,5-Dimethyl-2'-hydroxy-9 alpha-(3-methylbutyl)-6,7-benzomorphan, the 9 beta-analogue, and 9 alpha-N-substituted (N-ethyl, propyl, butyl, pentyl, hexyl, phenylethyl, allyl, and cyclopropylmethyl) compounds were synthesized and evaluated biochemically and pharmacologically. The 9 beta N-methyl compound was found to be as potent as morphine in the mouse hot plate assay and had one-seventh the affinity of morphine for the opioid receptor. The N-alkyl and N-phenethyl 9 alpha-substituted compounds were either inactive or relatively ineffective as antinociceptive agents. None of the examined compounds substituted for morphine in single-dose suppression studies in the rhesus monkey. The N-cyclopropylmethyl compound in the 9 alpha series had half the narcotic antagonist potency of nalorphine and one-eighth of its affinity for the opioid receptor. The 9 alpha-(3-methylbutyl) moiety, unlike bulky substituents in the 9 beta position of 6,7-benzomorphans, generally lowers affinity for the mu opioid receptor and diminishes their in vivo activity as agonists or antagonists.


Tapentadol in neuropathic pain cancer patients: a prospective open label study.
Many chemotherapy treatments induce peripheral neuropathy (CIPN). These patients often experience neuropathic pain (NP) that reduces the quality of life. The aim of this prospective, open label study was to evaluate the efficacy and tolerability of tapentadol (TP) in patients affected by CIPN. CIPN were consecutively enrolled in a prospective open label study at the Neuro-Oncology Unit of the Regina Elena National Cancer Institute in Rome. During the titration phase, each patient initially received doses of TP 50 mg twice a day. All patients underwent pain intensity (NRS) and DN4. For evaluation of quality of life, patients underwent EORTC QLQ-C30 and EORTC QLQ-CIPN2 QLQ-CIPN20. We enrolled 31 patients, 19 were females with a median age of 60 years. After 3 months of treatment with TP, 22 patients completed the statistical package for social sciences (SPSS). Nineteen patients out of 22 showed a response to treatment (86%). We also observed that TP reduced the NRS and DN4 values from baseline to the last visit in a significant way (p < 0.001, respectively). Seven patients (22.5%) discontinued the TP therapy after the first week of occurrence of side effects. Furthermore, we observed that TP improved also the global health status measured by EORT QLQ-C30. TP is well tolerated and efficacy in the treatment of NP. The important reduction of neuropathic pain, the improvement in NRS and QoL scores after therapy with TP makes it a candidate in the management of patients suffering from neuropathic pain of CIPN also as a first line of therapy.


Barriers to nurses' reporting of medication administration errors in Taiwan.
To describe nurses' perceptions of reporting barriers to reporting medication administration errors (MAE) and to examine the relationship between the barriers to MAE reporting and cultural factors and nursing work environment in Taiwan. A cross-sectional, descriptive correlational design with self-administered questionnaires was conducted in one large medical center hospital in southern Taiwan. The measurement tools included the Chinese versions of the Work Environment Questionnaire, Barriers to MAE Reporting, Index of Hierarchy of Authority, and Face-Concern scale. A mail survey of 807 nurses using the Total Design Method was implemented for data collection with 597 questionnaires used in data analyses. The major perceived barrier was fear. Regression analysis showed that power hierarchy, face-saving concern, and work environment factors (e.g., quality management and peer relations) accounted for 54.6% variance in the barriers. Age, educational background, working experience, experience of having made MAEs, and failure to report MAEs were not associated with the barriers. Taiwanese nurses perceived similar barriers to MAE reporting. The more power hierarchy and face-saving concern the nurses agreed on, the more barriers they perceived. The association between the barriers and nursing work environment was negative and weak.


Demonstration of a direct interaction between sigma-1 receptors and acid-sensing ion channels.
The sigma-1 receptor is a widely expressed protein that interacts with a variety of ion channels, including the acid-sensing ion channel (ASIC) 1a. Here we used atomic force microscopy to determine the architecture of the ASIC1a/sigma-1 receptor complex. When isolated His(8)-tagged ASIC1a was imaged in complex with anti-His(6) antibodies, the angle between pairs of bound antibodies was 135 degrees , consistent with the known trimeric structure of the channel. When ASIC1a was coexpressed with FLAG/His(6)-tagged sigma-1 receptor, ASIC1a became decorated with small particles, and pairs of these particles bound at an angle of 131 degrees . When these complexes were incubated with anti-FLAG antibodies, pairs of antibodies bound at an angle of 134 degrees , confirming that the small particles were sigma-1 receptors. Of interest, we found that the sigma-1 receptor ligand haloperidol caused an approximately 50% reduction in ASIC1a/sigma-receptor binding, suggesting a way in which sigma-1 ligands might modulate channel properties. For the first time, to our knowledge, we have resolved the structure of a complex between the sigma-1 receptor and a target ion channel, and demonstrated that the stoichiometry of the interaction is 1 sigma-1 receptor/1 ASIC1a subunit.


Targeting macrophages rescues age-related immune deficiencies in C57BL/6J geriatric mice.
Changes to innate cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), during aging in healthy or tumor-bearing hosts are not well understood. We compared macrophage subpopulations and MDSCs from healthy young (6-8 weeks) C57BL/6J mice to those from healthy geriatric (24-28 months) mice. Spleens, lymph nodes, and bone marrow of geriatric hosts contained significantly more M2 macrophages and MDSCs than their younger counterparts. Peritoneal macrophages from geriatric, but not young, mice co-expressed CD40 and CX3CR1 that are usually mutually exclusively expressed by M1 or M2 macrophages. Nonetheless, macrophages from geriatric mice responded to M1 or M2 stimuli similarly to macrophages from young mice, although they secreted higher levels of TGF-β in response to IL-4. We mimicked conditions that may occur within tumors by exposing macrophages from young vs. geriatric mice to mesothelioma or lung carcinoma tumor cell-derived supernatants. While both supernatants skewed macrophages toward the M2-phenotype regardless of age, only geriatric-derived macrophages produced IL-4, suggesting a more immunosuppressive tumor microenvironment will be established in the elderly. Both geriatric- and young-derived macrophages induced allogeneic T-cell proliferation, regardless of the stimuli used, including tumor supernatant. However, only macrophages from young mice induced T-cell IFN-γ production. We examined the potential of an IL-2/agonist anti-CD40 antibody immunotherapy that eradicates large tumors in young hosts to activate macrophages from geriatric mice. IL-2-/CD40-activated macrophages rescued T-cell production of IFN-γ in geriatric mice. Therefore, targeting macrophages with IL-2/anti-CD40 antibody may improve innate and T-cell immunity in aging hosts.


Mapping of the human RNASEL promoter and expression in cancer and normal cells.
2',5'-Oligoadenylate (2-5A)-dependent RNase L is a ubiquitous endoribonuclease of higher vertebrates that functions in the interferon (IFN) antiviral response by degrading both viral and cellular single-stranded RNA (ssRNA). In addition, the RNase L gene, RNASEL, was mapped to the hereditary prostate cancer 1 (HPC1) gene. Previous analyses of human RNASEL determined its exon/intron structure but lacked a description of the promoter region. We thus mapped the RNASEL transcriptional start site using 5'-rapid amplification of cDNA ends (5'-RACE) and primer extension methods with RNA from human histiocytic lymphoma U937 cells. The promoter sequence was analyzed for potential transcription factor binding sites. Although a canonical IFN-gamma activation site (GAS) element (TTCCAAGAA) was identified (nucleotides -155 to -147), there was only slight induction of RNASEL promoter-reporter activity or of endogenous RNase L expression in response to IFN-alpha or IFN-gamma. Several sites for tissue-specific and general promoters were observed, however, which could explain the widespread expression of RNase L in mammalian cells. Accordingly, RNase L levels were determined and compared in different human and rodent cancer and normal cell types using a radiolabeled 2-5A derivative. In addition, levels of RNase L were established in various normal human tissues and cell types by immunoblotting and immunohistochemistry. Our findings are the first description of the human RNASEL promoter that allows constituitive expression in a range of normal and neoplastic cell types.


Applying the Advancing Excellence in America's Nursing Homes Circle of Success to improving and sustaining quality.
Looking forward to the Quality Assurance Performance Improvement (QAPI) program to be implemented and required in 2014, and as nursing home staff provide care for residents with increasingly complex health issues, knowledge of how to implement quality improvement (QI) is imperative. The nursing home administrator and director of nursing (DON) provide overall leadership, but it is the primary responsibility of the DON and other registered nurse staff to implement and manage the day to day QI process. This article describes potential roles of nursing leaders and key components of a QI project using a pressure ulcer case study exemplar to illustrate a quality improvement process. The authors suggest specific methods that RN leaders can employ using the Advancing Excellence Campaign Circle of Success as an organizing framework along with evidence-based resources. Nursing home leaders could use this article as a guideline for implementing any clinical quality improvement process.


Is fecal microbiota transplantation (FMT) an effective treatment for patients with functional gastrointestinal disorders (FGID)?
Despite its high prevalence and significant effect on quality of life, the etiology of functional gastrointestinal disorders (FGID), and specifically irritable bowel syndrome (IBS), has yet to be fully elucidated. While alterations in immunity, motility, and the brain-gut axis have been implicated in disease pathogenesis, the intestinal microbiota are increasingly being shown to play a role and numerous studies have demonstrated significant differences from normal in the intestinal flora of patients with FGID, and between types of FGID. Fecal microbiota transplantation (FMT) is a curative therapy for Clostridium difficile infection (CDI), a disease hallmarked by intestinal dysbiosis, and FMT is now being explored as a means to also restore intestinal homeostasis in FGID. This review aims to investigate the role of intestinal microbiota in the pathogenesis of FGID, the implications of FMT for the treatment of FGID, and the challenges encountered in measuring response to a specific intervention in patients with FGID.


[Textual research on Fengqing Jixueteng (Kadsura interior A. C. Smith), Kunming Jixueteng (Millettia dielsiana Harms ex Diels) and Jixueteng (Spatholobus suberectus Dunn)].
Being a common materia medica, the confusion of Jixuetengcaused by the homonyms of different substances for Jixuetengis always very complicated. Fengqing JixuetengPaste was first created in the Qing Dynasty. Fengqing Jixuetengwas derived from the dried stems of a variety of species in KadsuraJuss. and SchisandraMichx. from Schisandracea; while Kunming Jixueteng, derived from the dried stem of Millettia dielsianaHarms ex Diels, was firstly recorded in the Zhi wu ming shi tu kao(Textual Research on Reality and Titles of Plants). The earliest records of Spatholobus suberectusDunn as the original plant of Jixuetengwas in Guang xi ben cao xuan bian(Selected Compilation of Chinese Materia Medica in Guangxi). It was not until 1997 that Spatholobus suberectusDunn was recorded as an origin of orthodox product of Jixuetengin the Chinese Pharmacopoeia. At present, the origins of Jixuetengis very complicated as recorded in different provincial standards, including three species of three genus from Leguminosae.The varieties of species from KadsuraJuss. and SchisandraMichx. had long been used as Fengqing Jixueteng, but currently the most extensively used one is Spatholobus suberectusDunn as Jixueteng. There are more differences in records of Jixuetengin history up to the present, hence, further investigation and research on Jixuetengis still necessary.


[Pretreatment and Posttreatment Evaluations of Circulating Tumor Cells(CTC)in Patients with Metastatic Breast Cancer].
Recently, circulating tumor cells (CTCs) of cancer patients have been analyzed as a biomarker of disease progression and as a new prognostic tool.We conducted a pilot study to determine whether CTCs present before and after chemotherapy or peptide vaccination predicted outcome in patients with metastatic breast cancer (MBC). CTCs were isolated from the peripheral blood of MBC patients and evaluated using the CellSearch®System (Janssen Diagnostics). The expression of the HLA classⅠ molecule in the CTCs was analyzed simultaneously by using a flow cytometric system. A CTC-positive test result was defined as five or more CTCs/7.5 mL blood. Nine patients (median [range] age, 64.2 years [44-80 years]) were included. Four (57.1%) of 7 MBC patients with Luminal A subtype tested positive for CTC.Of 6 MBC patients, 5 (83.3%) had a decreased mean number of CTCs, from 35.8/7.5 to 0.4/7.5 mL, after 3 courses of systemic chemotherapy. Furthermore, CTC-HLA class Ⅰexpression level was decreased in 2 (66.7%) of 3 patients after cytotoxic chemotherapy but increased in 4 (80.0%) of 5 patients after 6 vaccinations with tumor-specific peptide vaccines. The number of CTCs and CTC-HLA class Ⅰ expression level in the patients with MBC changed after the treatment with systemic chemotherapy or peptide-vaccine therapy.


Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.
The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies the changes made in the conductivity of a medium by the application of focused ultrasound. Recently, based on the AE effect, several biomedical imaging techniques have been widely studied, such as ultrasound-modulated electrical impedance tomography and ultrasound current source density imaging. To further investigate the mechanism of the AE effect in tissue and to provide guidance for such techniques, we have modeled the tissue AE effect using the theory of solid mechanics. Both bulk compression and thermal expansion of tissue are considered and discussed. Computation simulation shows that the muscle AE effect result, conductivity change rate, is 3.26×10-3 with 4.3-MPa peak pressure, satisfying the theoretical value. Bulk compression plays the main role for muscle AE effect, while thermal expansion makes almost no contribution to it. In addition, the AE signals of porcine muscle are measured at different focal positions. With the same magnitude order and the same change trend, the experiment result confirms that the simulation result is effective. Both simulation and experimental results validate that tissue AE effect modeling using solid mechanics theory is feasible, which is of significance for the further development of related biomedical imaging techniques.


Selective antibiotic prophylaxis in biliary surgery.
Wound infections and septic complications are among the most frequent complications of biliary surgery. Such complications frequently occur in patients with infected bile. The presence of infected bile is predictable and can be expected in patients defined as high-risk patients. Short-term perioperative antibiotic prophylaxis was shown to be effective on an unselective basis by several authors. In this study of 231 consecutive biliary procedures, antibiotic prophylaxis was used on a selective basis in high-risk patients only. The high-risk patients were 55% of the entire group. Perioperative prophylaxis was given for 24 hours using four gentamicin injections starting two hours prior to anesthesia. Selective prophylaxis was shown to be highly effective reducing the wound infection rate to 3.5% in this group, compared to 12.5% in a similar group without prophylaxis. The selective use of prophylaxis was shown to be highly cost-effective as compared to the group without prophylaxis as well as reported groups of unselective prophylaxis in biliary surgery.


A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis.
Oligoarticular onset juvenile idiopathic arthritis (JIA) has a variable disease course. In some patients the disease remains confined to a few joints (persistent oligoarticular) while in others it extends to affect more joints (oligoarticular extended). Osteopontin is thought to play a role in the pathogenesis. To investigate whether a polymorphic variant in the human osteopontin gene, which is in linkage disequilibrium with recently characterised promoter variants, is associated with the disease course in oligoarticular JIA. Genotyping of the two base pair insertion/deletion variant at +245 in the first intron was undertaken by polymerase chain reaction (PCR) amplification of DNA fragments, using a fluorescently labelled primer, followed by allele detection after rapid separation of PCR products on an automated DNA sequencer. Allele 2 of the polymorphic variant in the osteopontin first intron was significantly associated with the persistent oligoarticular form rather than the extended form of JIA. This was verified at the level of genotype and allele frequencies. The results suggest that osteopontin gene polymorphism is associated with the disease course in oligoarticular JIA and might therefore represent a useful genetic marker to characterise patients with oligoarticular JIA who are at risk of a worse outcome.


[Huang Yizhou's study on Nei jing (Inner Canon)].
Being a great classical scholar of the late Qing dynasty, Huang Yizhou collated Nei jing (Inner Canon) by textual criticism. But most of his works were missing. By reviewing historical documents and literature, it has been found that his collated books include Huang di nei jing su wen jiao ben (Collated Edition of Huangdi's Inner Canon Plain Questions), Huang di nei jing su wen chong jiao zheng (Recollated Huangdi's Inner Canon Plain Questions), Nei jing zhen ci (Acupuncture in Inner Canon), Huang di nei jing jiu juan ji zhu (Variorum of Nine Volumes of Huangdi's Inner Canon), Huang di nei jing ming tang (Acupuncture Chart of Huangdi's Inner Canon), and Jiu chao tai su jiao ben (Old Extremely Plain Question Recension). Many of his disciples became famous scholars in the Republican period.


Erythrocyte rosette formation of equine peripheral blood lymphocytes.
Erythrocyte rosette (ER) formation of equine peripheral blood lymphocytes (PBL) was characterized. Guinea pig and, to a lesser extent, human erythrocytes formed ER; cat, cow, dog, hamster, mouse, rat, and sheep erythrocytes showed negligible rosetting properties. Conditions of the assay were varied to determine which procedure allowed the largest percentage of rosette formation. The PBL from 20 normal horses were then assayed, averaging 38 +/- 2% ER. To characterize the erythrocyte receptor as being on T or B cells, equine thymocytes from 6 foals were assayed; the thymocytes formed an average of 66 +/- 5% ER. Mixed ER and erythrocyte-antibody-complement rosette assays showed no PBL which bound both ER and erythrocyte-antibody-complement rosettes. The PBL which was stimulated with phytohemagglutinin formed more rosettes (69 +/- 2%) than nonstimulated, control PBL (42 +/- 3%).


Association between the Temporomandibular Joint Morphology and Chewing Pattern.
This study aimed to investigate whether the morphology of the temporomandibular joint (TMJ) is associated with chewing patterns while considering skeletal morphology, sex, age, and symptoms of temporomandibular disorder (TMD). A cross-sectional observational study of 102 TMJs of 80 patients (age 16-40 years) was performed using pretreatment records of cone-beam computed tomography imaging of the TMJ, mandibular kinesiographic records of gum chewing, lateral and posteroanterior cephalometric radiographs, patient history, and pretreatment questionnaires. To select appropriate TMJ measurements, linear regression analyses were performed using TMJ measurements as dependent variables and chewing patterns as the independent variable with adjustment for other covariates, including Nasion-B plane (SNB) angle, Frankfort-mandibular plane angle (FMA), amount of lateral mandibular shift, sex, age, and symptoms of TMD. In multiple linear regression models adjusted for other covariates, the length of the horizontal short axis of the condyle and radius of the condyle at 135° from the medial pole were significantly (p < 0.05) associated with the chewing patterns in the frontal plane on the working side. "Non-bilateral grinding" displayed a more rounded shape of the mandibular condyle. Conversely, "bilateral grinding" exhibited a flatter shape in the anteroposterior aspect. These findings suggest that the mandibular condyle morphology might be related to skeletal and masticatory function, including chewing patterns.


Testing the Effect of Aggressive Beverage on the Damage of Enamel Structure.
Dental erosion is a common problem in modern societies, owing to the increased consumption of acid drinks such as soft drinks, sports drinks, fruit juice. Examining the enamel surface with the Atomic Force Microscopy (AFM) enables more precise registering and defining the changes of enamel surface structure and microhardness. This method can be used to compare the efficiency of application of different preventive and therapy materials and medicaments in dentistry. The chronic regular consumption of low pH cola drinks encouraged the erosion of the teeth. The loss of anatomy and sensitivity are direct results of acid cola dissolving coronal tooth material. Under the influence of coca cola, a change of crystal structure and nanomorphology on enamel surface occurs. This paper reflects dental damage from abusive cola drinking, and the clinical presentation can be explained from data presented in this thesis. The trial was conducted on a total of 40 extracted teeth which were divided into two groups treated with the solution of coca cola during 5 minutes, and then prepared and tested with a standard AFM procedure, type SPM-5200. Quantitative analysis was performed by comparing the roughness parameters (Ra) of the treated and non-treated sample. Based on the test of a hypothesis of the existence of differences between the treated and untreated sample, with an application of a t-test, it is shown that there are statistically highly significant differences between Ra of the treated sample with a 5-minute treatment of coca cola and Ra of the same sample without the treatment. Use of AFM enables successful monitoring of changes on enamel surface as well as the interpretation of the ultrastructural configuration of the crystal stage and the damage created under the influence of different external factors.


Effects of corn straw or mixed forage diet on rumen fermentation parameters of lactating cows using a wireless data logger.
The objective of this study was to evaluate the effect of two different forage types on rumen fermentation parameters and profiles using a wireless data logger. Eight lactating cows were randomly assigned to one of two dietary treatments with a low forage diet with corn straw (CS) or a high forage diet with mixed forage (MF) as the forage source, respectively. Dietary physically effective neutral detergent fiber (peNDF) content was 11.3% greater in CS. Dry matter intake and milk fatty acid content decreased upon CS (P < 0.05). Ruminal pH, temperature and oxidation reduction potential (ORP) were monitored for 14 weeks. The CS group had significantly higher pH but lower temperature and ORP compared to MF (P < 0.01). With the CS diet regime, pH at the time before morning feeding, rumination and post-ingestion were significantly higher than those in the MF group (P < 0.05). However, times with the ruminal pH below 6.0 and 5.8 were significantly reduced (P < 0.05), whereas ruminal pH below 5.6 tended to be lower (P = 0.07). The results indicated that rumen fermentation parameters were affected by forage types and dietary peNDF content might be predominant in ruminal pH regulation.


Photo-detectors integrated with resonant tunneling diodes.
We report on photo-detectors consisting of an optical waveguide that incorporates a resonant tunneling diode (RTD). Operating at wavelengths around 1.55 μm in the optical communications C band we achieve maximum sensitivities of around 0.29 A/W which is dependent on the bias voltage. This is due to the nature of RTD nonlinear current-voltage characteristic that has a negative differential resistance (NDR) region. The resonant tunneling diode photo-detector (RTD-PD) can be operated in either non-oscillating or oscillating regimes depending on the bias voltage quiescent point. The oscillating regime is apparent when the RTD-PD is biased in the NDR region giving rise to electrical gain and microwave self-sustained oscillations Taking advantage of the RTD's NDR distinctive characteristics, we demonstrate efficient detection of gigahertz (GHz) modulated optical carriers and optical control of a RTD GHz oscillator. RTD-PD based devices can have applications in generation and optical control of GHz low-phase noise oscillators, clock recovery systems, and fiber optic enabled radio frequency communication systems.


Methyl dynamics of a Ca2+-calmodulin-peptide complex from NMR/SRLS.
We developed the slowly relaxing local structure (SRLS) approach for analyzing NMR spin relaxation in proteins. SRLS accounts for dynamical coupling between the tumbling of the protein and the local motion of the probe and for general tensorial properties. It is the generalization of the traditional model-free (MF) method, which does not account for mode-coupling and treats only simple tensorial properties. SRLS is applied herein to ²H relaxation of ¹³CDH₂ groups in the complex of Ca(2+)-calmodulin with the peptide smMLCKp. Literature data comprising ²H T₁ and T₂ acquired at 14.1 and 17.6 T, and 288, 295, 308, and 320 K, are used. We find that mode-coupling is a small effect for methyl dynamics. On the other hand, general tensorial properties are important. In particular, it is important to allow for the asymmetry of the local spatial restrictions, which can be represented in SRLS by a rhombic local ordering tensor with components S(0)(2) and S(2)(2). The principal axes frame of this tensor is obviously different from the axial frames of the magnetic tensors. Here, we find that -0.2 ≤ S(0)(2) ≤ 0.5 and -0.4 ≤ S(2)(2) ≤ 0. MF features a single "generalized" order parameter, S, confined to the 0-0.316 range; the local geometry is inherently simple. The parameter S is inaccurate, having absorbed unaccounted for effects, notably S(2)(2) ≠ 0. We find that the methionine methyls (the other methyl types) reorient with rates of 8.6 × 10⁹ to 21.4 × 10⁹ (0.67 × 10⁹ to 6.5 × 10⁹) 1/s. The corresponding activation energies are 10 (10-27) kJ/mol. By contrast, MF yields inaccurate effective local motional correlation times, τ(e), with nonphysical temperature dependence. Thus, the problematic S- and τ(e)-based MF picture of methyl dynamics has been replaced with an insightful physical picture based on a local ordering tensor related to structural features, and a local diffusion tensor that yields accurate activation energies.


Antimicrobial resistance of nosocomial strain of Acinetobacter baumannii in Children's Medical Center of Tehran: a 6-year prospective study.
There are increasing reports of emergence of multiple drug resistant (MDR) Acinetobacter spp in the world; however there are a few reports in our country. 145 A. baumannii isolates from distinct wards and Children's Medical Center (CMC) in Tehran were studied in order to find the profile of antibiotic resistance among them. 40.6% (59/145) of A. baumannii isolates were identified as MDR. Overall susceptibility rates to cotrimoxazole, chloramphenicole and ciprofloxacin were 23.4%, 16.9% and 20.1%, respectively. Frequency susceptibility rates to amikacin, kanamycin, gentamycin and tobramycin decreased gradually from 81.2%, 50%, 50% and 62.5% in 2002 to 25%, 15.6%, 28.1% and 25% in 2007 respectively. Overall susceptibility rates to cephalosporines cephalotin, ceftazidime, cefteriaxon, ceftizoxime and cefixime were 9.3%, 14.7%, 16.2%, 15.9% and 18%, respectively. Susceptibility to carbapenems was assessed only in 2007. The susceptibility rates of Imipenem and meropenem were shown to be 50% and 46.8%, respectively. Our data indicates that MDR A. baumannii strains are spreading and carbapenem resistance is becoming more common in Iran. Our findings also highlight the importance of clinicians' access to updated susceptibility data regarding A. baumannii in developing countries such as Iran.


Zika, chikungunya and co-occurrence in Brazil: space-time clusters and associated environmental-socioeconomic factors.
Chikungunya and Zika have been neglected as emerging diseases. This study aimed to analyze the space-time patterns of their occurrence and co-occurrence and their associated environmental and socioeconomic factors. Univariate (individually) and multivariate (co-occurrence) scans were analyzed for 608,388 and 162,992 cases of chikungunya and Zika, respectively. These occurred more frequently in the summer and autumn. The clusters with the highest risk were initially located in the northeast, dispersed to the central-west and coastal areas of São Paulo and Rio de Janeiro (2018-2021), and then increased in the northeast (2019-2021). Chikungunya and Zika demonstrated decreasing trends of 13% and 40%, respectively, whereas clusters showed an increasing trend of 85% and 57%, respectively. Clusters with a high co-occurrence risk have been identified in some regions of Brazil. High temperatures are associated with areas at a greater risk of these diseases. Chikungunya was associated with low precipitation levels, more urbanized environments, and places with greater social inequalities, whereas Zika was associated with high precipitation levels and low sewage network coverage. In conclusion, to optimize the surveillance and control of chikungunya and Zika, this study's results revealed high-risk areas with increasing trends and priority months and the role of socioeconomic and environmental factors.


The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer.
There is little published data on the role of FOXP3 in gastric cancer. FOXP3 expression and localization in gastric cancer tissues and cells were examined by immunohistochemistry, RT-PCR, flow cytometry, western blot, and laser confocal microscopy. CCK8, plate clone, wound healing, and transwell insert assays were performed for gastric cancer cells. Potential molecules and signaling pathways were screened using high-throughput transcriptome sequencing. FOXP3 expression in gastric cancer tissues was higher than that in para-carcinoma tissues. It was restricted to the cytoplasm of para-carcinoma tissues, but was observed in the cytoplasm or/and nuclei of gastric cancer tissues. FOXP3 expression was positively correlated with pathological grading, and was detected in gastric cancer and GES-1 cells, where it was expressed in the cytoplasm alone, or in both the cytoplasm and the nucleus. FOXP3 overexpression promoted cell proliferation, migration, and invasion, while FOXP3 knockdown suppressed these effects. Furthermore, RT-PCR and ELISA confirmed that FOXP3 upregulation resulted in increased TGF-β expression and secretion in gastric cancer cells. FOXP3 expression was associated with degree of gastric cancer differentiation. In addition, upregulated and ectopic tumoral FOXP3 can promote gastric cancer proliferation, migration, and invasion, partly through the TGF-β pathway.


Monitoring and imaging the clot during systemic thrombolysis in stroke patients.
Intravenous thrombolysis is the only approved treatment for acute ischemic stroke when administered within the first 3 h of stroke onset. Response to systemic thrombolysis depends on several factors including the location of arterial occlusion, clot characteristics and, ultimately, the embolic source. In the last few years, tremendous progress has been made, resulting in the widespread implementation of noninvasive neurovascular techniques. These imaging modalities are being increasingly performed in the acute stroke setting, without substantial delay, in a large number of centers worldwide. Transcranial Doppler ultrasound provides a unique opportunity to assess several aspects of clot dissolution by means of continuous monitoring of recanalization during and after tissue plasminogen activator administration. This approach allows for the evaluation of patients at the bedside and in real time due to the commencement, timing, speed and degree of artery reopening in addition to allowing the documentation of reocclusion after successful recanalization. Gradient refocused echo susceptibility vessel sign (GRE SVS) magnetic resonance imaging may be particularly useful for the identification of an intravascular thrombus during the acute phase of ischemic stroke; GRE SVS may represent a surrogate of clot composition and differential response to thrombolysis. The increasing availability of advanced neurovascular techniques may, in the near future, improve the design of stroke trials. The capability of these techniques to assess not only tissue viability but also key aspects regarding susceptibility to thrombolysis such as location, amount, composition, and age of the offending clot may improve the safety and efficacy profile of thrombolytic therapy for acute ischemic stroke.


Regiospecificity of human cytochrome P450 1A1-mediated oxidations: the role of steric effects.
Cytochrome P450 1A1 oxidizes a diverse range of substrates, including the procarcinogenic xenobiotic benzo[a]pyrene (B[a]P) and endogenous fatty acid precursors of prostaglandins, such as arachidonic acid (AA) and eicosapentaenoic acid (EA). We have investigated the extent to which enzyme-substrate interactions govern regio- and stereoselectivity of oxidation of these compounds by using docking and molecular dynamics (MD) simulations to examine the likelihood of substrate oxidation at various sites. Due to structural differences between the substrates analyzed, B[a]P and its diols (planar, rigid), and the fatty acids AA and EA (long, flexible), different docking strategies were required. B[a]P, B[a]P-7,8-diols, (+) 7S,8S- and (-) 7R,8R-diols, were docked into the active site of a homology model of P450 1A1 using an automated routine, Affinity (Accelrys, San Diego, CA). AA and EA, on the other hand, required a series of restrained MD simulations to obtain a variety of productive binding modes. All complexes were evaluated by MD-based in silico site scoring to predict product profiles based on certain geometric criteria, such as angle and distance of a given substrate atom from the ferryl oxygen. For all substrates studied, the in vitro profiles were generally reflected by the in silico scores, which suggests that steric factors play a key role in determining regiospecificity in P450 1A1-mediated oxidations. We have also shown that molecular dynamics simulations may be very useful in determination of product profiles for structurally diverse substrates of P450 enzymes.


[Ocular ischemic syndrome--a case report].
Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.


Combined microfluidic-micromagnetic separation of living cells in continuous flow.
This paper describes a miniaturized, integrated, microfluidic device that can pull molecules and living cells bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and thus selectively remove them from flowing biological fluids without any wash steps. To accomplish this, a microfabricated high-gradient magnetic field concentrator (HGMC) was integrated at one side of a microfluidic channel with two inlets and outlets. When magnetic micro- or nano-particles were introduced into one flow path, they remained limited to that flow stream. In contrast, when the HGMC was magnetized, the magnetic beads were efficiently pulled from the initial flow path into the collection stream, thereby cleansing the original fluid. Using this microdevice, living E. coli bacteria bound to magnetic nanoparticles were efficiently removed from flowing solutions containing densities of red blood cells similar to that found in blood. Because this microdevice allows large numbers of beads and cells to be sorted simultaneously, has no capacity limit, and does not lose separation efficiency as particles are removed, it may be especially useful for separations from blood or other clinical samples. This on-chip HGMC-microfluidic separator technology may potentially allow cell separations to be carried out in the field outside of hospitals and clinical laboratories.


Documentation and treatment outcomes of smear-negative and extra-pulmonary tuberculosis in Ethiopia.
Smear-negative and extra-pulmonary tuberculosis (TB) comprise two thirds of TB cases reported in Ethiopia. Neither treatment outcomes nor underlying associated factors are routinely reported for these cases. To assess treatment outcomes and associated risk factors of smear-negative and extra-pulmonary TB in comparison with smear-positive cases. Record review of all TB cases registered in 14 randomly selected public and private health facilities in Addis Ababa, Ethiopia, over a 1-year period. Percentages of smear-negative and extra-pulmonary TB were independent of human immunodeficiency virus (HIV) status, and were not evenly distributed among health facilities. Extra-pulmonary TB was overrepresented in the private sector, and smear-negative TB was more frequent in health clinics than in hospitals. Outcomes reported by clinics were more favourable than those of the hospitals; no differences were observed when comparing public and private health facilities. Only 54% of the TB registers were complete; missing information correlated with unfavourable outcomes. Younger age, but not sex or HIV status, was associated with favourable outcomes. The uneven distribution of smear-negative and extra-pulmonary TB among different health facilities requires further study and may provide important insight into diagnosis and care of these patients. Incomplete TB register information may be an underappreciated factor contributing to unfavourable outcomes.


Straight leg raising test and lumbar cerebrospinal fluid levels of vasoactive intestinal polypeptide and somatostatin in patients with low back pain.
Straight leg raising was recorded before myelography in 77 patients. At myelography, samples of cerebrospinal fluid were drawn and later analyzed for neuropeptides vasoactive intestinal polypeptide and somatostatin. The study sought to examine correlations, if any, between a positive straight leg raising test and cerebrospinal fluid neuropeptide levels. The straight leg raising test was recorded for all patients before a myelography examination was performed because of intractable leg pain symptoms. Forty-seven of the patients were men and 30 were women. Cerebrospinal fluid samples were obtained from all patients upon myelography. Levels of the neuropeptides vasoactive intestinal polypeptide and somatostatin were analyzed in a blind manner by radioimmunoassay, using commercially available radioimmunoassay kits. The results are compatible with previous observations that suggest cerebrospinal neuropeptide levels are altered in conjunction with neural injury or pain syndromes. In the present mixed back pain patient population, which included radicular pain symptoms due to disc herniation and lumbar stenosis, alterations in vasoactive intestinal peptide levels in particular were observed with a positive straight leg raising test. Nerve root injury, as suggested by a positive straight leg raising test, appears to be neurochemically linked to altered cerebrospinal fluid vasoactive intestinal peptide levels.


Mammalian skin cell biology: at the interface between laboratory and clinic.
Mammalian skin research represents the convergence of three complementary disciplines: cell biology, mouse genetics, and dermatology. The skin provides a paradigm for current research in cell adhesion, inflammation, and tissue stem cells. Here, I discuss recent insights into the cell biology of skin. Single-cell analysis has revealed that human epidermal stem cells are heterogeneous and differentiate in response to multiple extrinsic signals. Live-cell imaging, optogenetics, and cell ablation experiments show skin cells to be remarkably dynamic. High-throughput, genome-wide approaches have yielded unprecedented insights into the circuitry that controls epidermal stem cell fate. Last, integrative biological analysis of human skin disorders has revealed unexpected functions for elements of the skin that were previously considered purely structural.


Fistula output microorganism-susceptible antimicrobial prophylaxis is associated with a lower risk of surgical site infection in gastrointestinal fistula patients undergoing one-stage definitive surgery.
Empiric broad-spectrum antimicrobial prophylaxis (AMP) may not be sufficient to minimize the risk of surgical site infections (SSIs) after definitive surgical treatment of gastrointestinal (GI) fistula. This study investigates whether AMP targeted toward fistula microbiology is associated with a lower risk of SSIs in GI fistula patients undergoing one-stage definitive surgery. Fistula output was sampled from the abdominal fistula opening for microbial growth and drug sensitivity prior to surgery. The primary outcome measure was the overall incidence rate of SSIs. A total of 191 patients were examined. Pre-operative microbial culture identified microbial growth in 149 patients (76.0%). Post-operative SSIs occurred in 51 patients (26.7%). Risk index category, abdominal incision length, and time of peritoneal drain removal had significantly negative impacts on SSIs frequency. Sensitive AMP agents were associated with a significantly lower risk of SSIs, compared with insensitive AMP agents, but with a similar risk to indefinite AMP agents (23.2% vs. 45.2% vs. 23.1%; odds ratio [95% confidence interval]: 2.724 [1.063, 6.979], p=0.034; 1.008 [0.467-2.177], p=0.984). Antimicrobial prophylaxis targeted toward fistula output AMP may minimize the occurrence of SSIs after one-stage definitive surgical treatment of GI fistula.


Nest-site selection of passerines: effects of geographic scale and public and personal information.
Nest-site selection is an important determinant of individual fitness in birds. Understanding what information individuals use to choose nest sites is therefore important for understanding the evolution of nest-site selection, the dynamics of populations, and the conservation of species. We used five years of mark-recapture data for Mountain Bluebirds (Sialia currucoides) to examine how dispersal probability and nest-site selection vary with potential cues of nest-site quality. Dispersal distance between breeding seasons and nest-site selection were modeled as a function of personal reproductive success, conspecific density, conspecific reproductive success, and habitat type. Between years, the dispersal probability was related to personal reproductive success, not conspecific information, and individuals fledging fewer young dispersed longer distances. For dispersing individuals, the probability that a nest site was selected in year i was negatively related to distance from the nest site selected in year i - 1 for all age and sex classes, and positively related to conspecific density and reproductive success in year i - 1 for both second-year (SY) and after-hatch-year (AHY) females. However, nest-site selection in year i was more strongly related to conspecific density in year i- 1 for hatch-year (HY) females and was much more strongly related to the reproductive success of conspecifics in year i - 1 for AHY females. Nest-site selection of HY and AHY males was not consistently related to the metrics of conspecific information, but we suspect that relationships were obscured by competitive interactions. We found no evidence indicating that individuals respond differently to conspecific information at longer distances, suggesting that individuals limit dispersal to areas where they have prior knowledge. We predict that these patterns of nest-site selection will allow birds to loosely track nest-site quality and maintain an ideal free distribution, where average fitness is equal in all habitat types.


Physical Violations of the Bulk-Edge Correspondence in Topological Electromagnetics.
In this Letter, we discuss two general classes of apparent violations of the bulk-edge correspondence principle for continuous topological photonic materials, associated with the asymptotic behavior of the surface modes for diverging wave numbers. Considering a nonreciprocal plasma as a model system, we show that the inclusion of spatial dispersion (e.g., hydrodynamic nonlocality) formally restores the bulk-edge correspondence by avoiding an unphysical response at large wave numbers. Most importantly, however, our findings show that, for the considered cases, the correspondence principle is physically violated for all practical purposes, as a result of the unavoidable attenuation of highly confined modes even if all materials are assumed perfect, with zero intrinsic bulk losses, due to confinement-induced Landau damping or nonlocality-induced radiation leakage. Our work helps clarifying the subtle and rich topological wave physics of continuous media.


Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with Corresponding Human Data.
The research for high-throughput diagnostic tests for victims of radio/nuclear incidents remains ongoing. In this context, we have previously identified candidate genes that predict risk of late-occurring hematologic acute radiation syndrome (HARS) in a baboon model. The goal of the current study was to validate these genes after radiation exposure in humans. We also examined ex vivo relative to in vivo measurements in both species and describe dose-response relationships. Eighteen baboons were irradiated in vivo to simulate different patterns of partial- or total-body irradiation (TBI), corresponding to an equivalent dose of 2.5 or 5 Sv. Human in vivo blood samples were obtained from patients exposed to different dose ranges: diagnostic computerized tomography (CT; 0.004-0.018 Sv); radiotherapy for prostate cancer (0.25-0.3 Sv); and TBI of leukemia patients (2 × 1.5 or 2 × 2 Sv, five patients each). Peripheral whole blood of another five baboons and human samples from five healthy donors were cultivated ex vivo and irradiated with 0-4 Sv. RNA was isolated pairwise before and 24 h after irradiation and converted into cDNA. Gene expression of six promising candidate genes found previously by us in a baboon model ( WNT3, POU2AF1, CCR7, ARG2, CD177, WLS), as well as three genes commonly used in ex vivo whole blood experiments ( FDXR, PCNA, DDB2) was measured using qRT-PCR. We confirmed the six baboon candidate genes in leukemia patients. However, expression for the candidate gene FDXR showed an inverse relationship, as it was downregulated in baboons and upregulated in human samples. Comparisons among the in vivo and ex vivo experiments revealed the same pattern in both species and indicated peripheral blood cells to represent the radiation-responsive targets causing WNT3 and POU2AF1 gene expression changes. CCR7, ARG2, CD177 and WLS appeared to be altered due to radiation-responsive targets other than the whole blood cells. Linear dose-response relationships of FDXR, WNT3 and POU2AF1 using human ex vivo samples corresponded with human in vivo samples, suggesting that ex vivo models for in vivo dose estimates can be used over a wide dose range (0.001-5 Sv for POU2AF1). In summary, we validated six baboon candidate genes in humans, but the FDXR measurements underscored the importance of independent assessments even when candidates from animal models have striking gene sequence homology to humans. Since whole blood cells represented the same radiation-responsive targets for FDXR, WNT3 and POU2AF1 gene expression changes, ex vivo cell culture models can be utilized for in vivo dose estimates over a dose range covering up to 3.5 log scales. These findings might be a step forward in the development of a gene expression-based high-throughput diagnostic test for populations involved in large-scale radio/nuclear incidents.


Incidence of chronic neuropathic pain subsequent to surgical removal of impacted third molars.
To determine the incidence of atypical odontalgia/chronic neuropathic pain subsequent to surgical removal of impacted third molars, a telephone survey and a clinical investigation were carried out. Patients operated on for impacted mandibular third molars during 1994 96 in the Oral Surgery Clinic. School of Dentistry, University of Bergen, Bergen, Norway, were contacted by telephone. Answers were obtained from 1035 (71%) out of a total of 1458 operated patients. Median observation time was 5 years 9 months, ranging from 4 years 5 months to 6 years 9 months. All except 23 (2.2%) patients stated that they had no long-term symptoms or problems from the surgical site, jaw, or face after the third molar removal. These 23 patients were all examined clinically and radiologically, and symptoms and findings were evaluated. Seventeen patients had TMJ dysfunction: primarily pain of muscular and joint origin. Three patients had a periodontal problem associated with the adjacent second molar, with deep bony pockets and recurrent periodontal infection while two had chronic pulpitis of a second molar. One patient reported a temporary maxillary pain after removal of an ipsilateral mandibular third molar. None of the patients met the criteria for a diagnosis of atypical odontalgia/neuropathic pain. A 95% confidence interval of 0-0.38% of incidence rate of postoperative neuropathic pain was calculated. It is concluded that atypical odontalgia/ chronic neuropathic pain subsequent to surgical third molar removal is rare.


Detection of Leishmania RNA virus 1 proteins.
Polyclonal antiserum was raised against the peak viral fraction of a sucrose gradient from LRV1-4-infected cells and used in Western immunoblot analysis to identify viral proteins from various isolates. Consistent with this result, in vitro-translated protein from cloned RNA was immunoprecipitated with the same antiserum. The putative capsid at times appeared as a doublet; relative amounts of the two species varied, depending on the method of purification.


Synthesis of Upconverting Hydrogel Nanocomposites Using Thiol-Ene Click Chemistry: Template for the Formation of Dendrimer-Like Gold Nanoparticle Assemblies.
The synthesis of upconverting hydrogel nanocomposites by base-catalyzed thiol-ene click reaction between 10-undecenoic acid capped Yb(3+)/Er(3+)-doped NaYF4 nanoparticles and pentaerythritol tetrakis(3-mercaptopropionate) (PETMP) as tetrathiol monomer is reported. This synthetic strategy for nanocomposite gels is quite different from works where usually the preformed gels are mixed with the nanoparticles. Developing nanocomposites by surface modification of capping ligands would allow tuning and controlling of the separation of the nanoparticles inside the gel network. The hydrogel nanocomposites prepared by thiol-ene click reaction show strong enhancement in luminescence intensity compared to 10-undecenoic acid-capped Yb(3+)/Er(3+)-doped NaYF4 nanoparticles through the upconversion process (under 980 nm laser excitation). The hydrogel nanocomposites display strong swelling characteristics in water resulting in porous structures. Interestingly, the resulting nanocomposite gels act as templates for the synthesis of dendrimer-like Au nanostructures when HAuCl4 is reduced in the presence of the nanocomposite gels.


Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct.
There are only a few reports of the influence of imposed flow on an active lymph pump under conditions of controlled intraluminal pressure. Thus, the mechanisms are not clearly defined. Rat mesenteric lymphatics and thoracic ducts were isolated, cannulated and pressurized. Input and output pressures were adjusted to impose various flows. Lymphatic systolic and diastolic diameters were measured and used to determine contraction frequency and pump flow indices. Imposed flow inhibited the active lymph pump in both mesenteric lymphatics and in the thoracic duct. The active pump of the thoracic duct appeared more sensitive to flow than did the active pump of the mesenteric lymphatics. Imposed flow reduced the frequency and amplitude of the contractions and accordingly the active pump flow. Flow-induced inhibition of the active lymph pump followed two temporal patterns. The first pattern was a rapidly developing inhibition of contraction frequency. Upon imposition of flow, the contraction frequency immediately fell and then partially recovered over time during continued flow. This effect was dependent on the magnitude of imposed flow, but did not depend on the direction of flow. The effect also depended upon the rate of change in the direction of flow. The second pattern was a slowly developing reduction of the amplitude of the lymphatic contractions, which increased over time during continued flow. The inhibition of contraction amplitude was dependent on the direction of the imposed flow, but independent of the magnitude of flow. Nitric oxide was partly but not completely responsible for the influence of flow on the mesenteric lymph pump. Exposure to NO mimicked the effects of flow, and inhibition of the NO synthase by N (G)-monomethyl-L-arginine attenuated but did not completely abolish the effects of flow.


Infusing gerontology into grades 7-12 social studies curricula.
This paper describes a model process to increase the exposure of middle and high school students to information on aging so they better understand the implications of an aging population and the stereotypes of older adults. A college Gerontology Institute, a social studies teacher education faculty member, and middle/high school social studies teachers collaborated on a program to develop and implement lesson plans that incorporate information on aging into existing courses. Institute staff provided expertise on gerontology and student teachers assisted in writing lesson plan objectives. Teachers developed about a dozen lessons covering from one class to two weeks in subjects such as global history, participation in government, Western civilizations, economics, and government. This experience suggests a number of issues that should be addressed when developing a gerontology infusion initiative with school teachers. Information on aging can be successfully incorporated into existing school curricula within the constraints of mandated learning objectives.


Endogenous viruses of parasitic wasps: variations on a common theme.
In a remarkable example of convergent evolution, several parasitic wasp lineages have independently captured and maintained complex DNA virus machineries, used to transfer virulence factors. Parasitic wasps, which develop inside the larvae of their insect hosts, may inject Polydnaviruses (PDVs) or Virus-Like particles (VLPs), derived from the recurrent endogenization of several large DNA viruses. PDVs evolved from the domestication in braconid and ichneumonid wasps of viruses from different families and function as gene transfer agents. In contrast, the independent domestication of nudiviruses led to the evolution of both PDV and VLP strategies. In Venturia canescens, the endogenous nudivirus has lost the ability to encapsidate DNA, instead VLPs cargo virulence molecules of wasp origin to the parasitized host.


HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: analysis of survival and remission duration.
Results of HLA-identical allogeneic marrow transplantation were analyzed for 66 patients with accelerated-phase chronic myelogenous leukemia (CML). Multivariate proportional hazards regression models were used to determine disease-related and transplant-related factors associated with posttransplant mortality and relapse. The projected 5-year survival rate was estimated at 18% by the product-limit method. The major causes of death were interstitial pneumonia, infection, and relapse. Splenomegaly at initial diagnosis and longer time interval from diagnosis to transplant were associated with decreased overall survival and event-free survival. Sixteen patients have relapsed between 17 and 1,569 days (median, 486) posttransplant. The use of T-cell-depleted marrow and older age of the donor or recipient were associated with an increased probability of leukemic relapse. Ten of the 16 relapses occurred among the 15 patients who received T-cell-depleted marrow. The actuarial relapse risk 2.5 years posttransplant was 100% in patients administered T-cell-depleted marrow as compared with 25% in patients administered unmodified marrow. The data in this report emphasize the increased risks and relatively poor results that occur when marrow transplantation is deferred until after signs of acceleration appear. When compared with results for patients who received transplants during chronic phase, the poor results seen here in patients administered unmodified marrow stem primarily from increased transplant-related mortality rather than increased relapse risk. The strikingly increased relapse rate associated with the use of T-cell depletion would discourage its use for graft-v-host disease prevention in patients who receive transplants for CML.


Development of High-Resolution Melting Curve Analysis for rapid detection of SEC23B gene mutation causing Congenital Dyserythropoietic Anemia type II in Indian population.
Congenital dyserythropoietic anemias (CDAs) are a very rare and heterogeneous group of disorders characterized by ineffective erythropoiesis. CDA II is caused by mutations in the SEC23B gene. The most common mutation reported in India is c.1385 A > G, p.Y462C. There is no simple and cost-effective confirmatory diagnostic test available for CDA, and therefore, many patients remain undiagnosed. High-resolution melting curve (HRM) analysis is a polymerase chain reaction (PCR) based technique applied to identify genetic differences and scan nucleic acid sequences. HRM can be used to rapidly screen the common mutation causing CDA II in the Indian population. Thus, we studied the use of High-Resolution Melting Curve Analysis to detect common mutation causing CDA II in the Indian population. 11 patients having SEC23B (Y462C) mutation causing CDA II are considered for this study. HRM was used to check the presence of Y462C mutation. To verify the accuracy of the HRM analysis, we compared HRM results with the results of Sanger sequencing. This helped us to confirm the diagnosis. We have described the clinical, hematological, and genetic data of eleven patients suffering from CDAII. According to HRM and Sanger sequencing, a homozygous SEC23B (Y462C) mutation was present in all patients, whereas a heterozygous Y462C mutation was present in their parents. Our data showed that High-Resolution Melting (HRM) analysis could be used to rapidly screen common SEC23B mutation that causes CDA II in the Indian population.


Atmospheric wet deposition of sulfur and nitrogen in Jiuzhaigou National Nature Reserve, Sichuan Province, China.
In the last two decades, remarkable ecological changes have been observed in Jiuzhaigou National Nature Reserve (JNNR). Some of these changes might be related to excessive deposition of sulfur (S) and nitrogen (N), but the relationship has not been quantified due to lack of monitoring data, particularly S and N deposition data. In this study, we investigated the concentrations, fluxes, and sources of S and N wet deposition in JNNR from April 2010 to May 2011. The results show that SO4(2-), NO3-, and NH4+ concentrations in the wet deposition were 39.4-170.5, 6.2-34.8, and 0.2-61.2 μeq L(-1), with annual Volume-Weighted Mean (VWM) concentrations of 70.5, 12.7, and 13.4 μeq L(-1), respectively. Annual wet deposition fluxes of SO4(2-), NO3-, and NH4+ were 8.06, 1.29, and 1.39 kg S(N)ha(-1), respectively, accounting for about 90% of annual atmospheric inputs of these species at the monitoring site. The results of Positive Matrix Factorization (PMF) analysis show that fossil fuel combustion, agriculture, and aged sea salt contributed to 99% and 83% of annual wet deposition fluxes of SO4(2-) and NO3-, respectively. Agriculture alone contributed to 89% of annual wet deposition flux of NH4+. Although wet deposition in JNNR was polluted by anthropogenic acids, the acidity was largely neutralized by the Ca2+ from crust and 81% of wet deposition samples had a pH higher than 6.00. However, acid rain mainly caused by SO4(2-) continued to occur in the wet season, when ambient alkaline dust concentration was lower. Since anthropogenic emissions have elevated S and N deposition and caused acid rain in JNNR, further studies are needed to better quantify the regional sources and ecological effects of S and N deposition for JNNR.


Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding proteins.
TNF-alpha induces the expression of IL-2R and promotes the proliferation and differentiation of T and B cells. In this report, we have studied the biochemical basis for TNF-alpha activation of the IL-2R alpha (Tac, p55) gene. Transfection of human T cell lines with selectively mutated forms of the IL-2R alpha promoter revealed that a kappa B element (nucleotides -267 to -256), as well as 5' flanking sequences (nucleotides -281 to -271) are required for TNF-alpha induction of this transcriptional unit. DNA binding studies demonstrated that this IL-2R alpha kappa B control element is specifically bound by a set of TNF-alpha inducible T cell nuclear proteins of relative Mr 80 to 90, 50 to 55, and 38 to 42 kDa. This protein recognition site from the IL-2R alpha promoter, as well as related kappa B motifs from the long terminal repeat of the type I human immunodeficiency virus, proved sufficient to impart TNF-alpha inducibility to an unresponsive heterologous promoter. These findings suggest that TNF-alpha-stimulated expression of the IL-2R alpha gene involves the induction of specific DNA binding proteins that in turn interact with a kappa B-like promoter element and facilitate activation of this transcription unit.